OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

BACKGROUND:Maxillofacial bone three-dimensional(3D)printing technology has been widely used in clinical diagnosis and treatment,but the data source before performing maxillofacial bone 3D printing mainly comes from the CT scanning data.The lens,thyroid and other parts of the human body are extremely sensitive to X-rays;therefore,it is particularly important to effectively reduce the dose of CT radiation when acquiring the data source.OBJECTIVE:To explore the feasibility of low-dose CT technology in optimizing radiation dose for maxillofacial bone 3D printing.METHODS:The medical records of 65 patients who underwent maxillofacial bone 3D printing in the Department of Stomatology at the General Hospital of Northern Theater Command from March 2021 to December 2023 were retrospectively collected and categorized into a conventional CT-dose 3D printing group(conventional CT-dose,120 kVp,automated tube current modulation,n=32)and a low-CT-dose 3D printing group(low-CT-dose group,80 kVp,automated tube current modulation,n=33).The effective dose of radiation was calculated and compared between the two groups.A Likert scale was used to evaluate the quality of 3D printing in the two groups,and the measurement bias and consistency between evaluators were measured using the Bland-Altman method.RESULTS AND CONCLUSION:(1)There was no significant difference in the general demographic characteristics(age,height,weight,body mass,sex,and body mass index)between the two groups(all P＞0.05).(2)The effective dose value of the low CT-dose 3D printing group was(0.3±0.1)mSv,which was about 62.5％lower than that in the conventional CT-dose 3D printing group[(0.8±0.1)mSv].(3)There was no significant difference in the subjective scoring of 3D printing quality between the two groups(all P＞0.05).The subjective consistency among evaluators was good,with Kappa values of 0.85,0.80,and 0.76.The scatter points in the Bland-Altman for both protocols were uniformly distributed within the standard deviation line,indicating good consistency between the two groups.To conclude,low-dose CT technology can be effectively applied in maxillofacial bone 3D printing,reducing radiation dose without affecting the quality of 3D printing.

BACKGROUND:Maxillofacial bone three-dimensional(3D)printing technology has been widely used in clinical diagnosis and treatment,but the data source before performing maxillofacial bone 3D printing mainly comes from the CT scanning data.The lens,thyroid and other parts of the human body are extremely sensitive to X-rays;therefore,it is particularly important to effectively reduce the dose of CT radiation when acquiring the data source.OBJECTIVE:To explore the feasibility of low-dose CT technology in optimizing radiation dose for maxillofacial bone 3D printing.METHODS:The medical records of 65 patients who underwent maxillofacial bone 3D printing in the Department of Stomatology at the General Hospital of Northern Theater Command from March 2021 to December 2023 were retrospectively collected and categorized into a conventional CT-dose 3D printing group(conventional CT-dose,120 kVp,automated tube current modulation,n=32)and a low-CT-dose 3D printing group(low-CT-dose group,80 kVp,automated tube current modulation,n=33).The effective dose of radiation was calculated and compared between the two groups.A Likert scale was used to evaluate the quality of 3D printing in the two groups,and the measurement bias and consistency between evaluators were measured using the Bland-Altman method.RESULTS AND CONCLUSION:(1)There was no significant difference in the general demographic characteristics(age,height,weight,body mass,sex,and body mass index)between the two groups(all P＞0.05).(2)The effective dose value of the low CT-dose 3D printing group was(0.3±0.1)mSv,which was about 62.5％lower than that in the conventional CT-dose 3D printing group[(0.8±0.1)mSv].(3)There was no significant difference in the subjective scoring of 3D printing quality between the two groups(all P＞0.05).The subjective consistency among evaluators was good,with Kappa values of 0.85,0.80,and 0.76.The scatter points in the Bland-Altman for both protocols were uniformly distributed within the standard deviation line,indicating good consistency between the two groups.To conclude,low-dose CT technology can be effectively applied in maxillofacial bone 3D printing,reducing radiation dose without affecting the quality of 3D printing.

Objective To explore the clinical value of albumin-globulin ratio(AGR)combined with prostate-specific antigen(PSA)and Gleason score in predicting biochemical recurrence(BCR)after radical resection in patients with localized prostate cancer, and to provide reference for early identification of BCR high-risk patients and individualized treatment. Methods The clinical data of 114 patients with localized prostate cancer treated during Sep.2019 and Sep.2023 were retrospectively analyzed.According to postoperative BCR status, patients were divided into the BCR group(n=43)and non-BCR group(n=71).Preoperative clinical and pathological data were compared between the two groups.Univariate and multivariate Cox regression analyses were used to assess the correlation between these indicators and BCR.The predictive performance of the combined model was evaluated using receiver operating characteristic(ROC)curve.The Kaplan-Meier method was used to compare biochemical recurrence-free survival(BFS)among patients with different AGR, PSA levels and Gleason scores.Results Compared with the non-BCR group, the BCR group had significantly higher PSA level and ISUP grading, but significantly lower AGR level(P＜0.001).Multivariate Cox regression analyses showed that AGR was negatively correlated with BCR(HR=0.031, 95%CI:0.008-0.119, P＜0.001), PSA was positively correlated with BCR(HR=1.009, 95%CI:1.002-1.016, P=0.017), and Gleason score was positively correlated with BCR(HR=1.551, 95%CI:1.199-2.005, P＜0.001).The area under the ROC curve(AUC)for the combined prediction model(AGR + PSA + Gleason score)was 0.886, with a sensitivity of 90.7% and a specificity of 78.9%.Kaplan-Meier analyses showed that patients in the low AGR group, high PSA group, and high Gleason score group had significantly lower BFS than those in the high AGR group, low PSA group and low Gleason score group, respectively(all P＜0.0001).Conclusion The combination of AGR, PSA and Gleason score is closely associated with postoperative BCR in patients with localized prostate cancer.The combined prediction model demonstrates high predictive efficacy and can provide an important reference for the early identification of high-risk BCR patients and for guiding individualized postoperative treatment.

ObjectiveTo investigate the potential targets of 2，5-dihydroxybenzoic acid （2，5-DHBA） in the treatment of metabolic dysfunction-associated fatty liver disease （MAFLD） and the molecular mechanism by which it regulates the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA network pharmacology analysis was performed at first， and related databases were used to obtain the common action targets of 2，5-DHBA and MAFLD， followed by molecular docking and pathway enrichment analysis to predict the potential biological processes and signaling pathways regulated by these targets. Then mouse normal hepatocytes AML-12 were used for cell experiments， and CCK-8 assay was used to determine the three optimal intervention concentrations of 2，5-DHBA. AML-12 cells were divided into control group， model group （cells cultured in a medium containing 2 mmol/L free fatty acid ［FFA］ to establish a cell model of MAFLD）， and three 2，5-DHBA intervention groups （cells cultured with FFA and 2，5-DHBA at the three different concentrations of 1.25， 5， and 20 μmol/L， respectively）. Oil red O staining was used to observe intracellular lipid accumulation； the fluorescent probe DCFH-DA was used to measure the level of intracellular reactive oxygen species （ROS）； biochemical assays were used to measure the content of triglyceride （TG） and total cholesterol （TC）； quantitative real-time PCR and Western Blot were used to measure the expression levels of related genes and proteins. A one-way analysis of variance was used for comparison between multiple groups， and the Tukey’s test was used for further comparison between two groups. ResultsA total of 32 common targets were obtained for 2，5-DHBA and MAFLD. Within a concentration range of 1.25 — 20 μmol/L， 2，5-DHBA treatment， starting from the concentration of 2.5 μmol/L， increased the viability of AML-12 cells in a dose-dependent manner. The minimum effective concentration of 1.25 μmol/L， the intermediate gradient concentration of 5 μmol/L， and the maximum safe concentration within the effective range of 20 μmol/L were selected for low-， middle-， and high-dose intervention， respectively. Compared with the model group， 2，5-DHBA intervention at concentrations of 1.25， 5， and 20 μmol/L could significantly reduce lipid droplet accumulation in cells （all P<0.05）， and there were significant differences in TG and TC between the model group and the three intervention groups （all P<0.05）. Compared with the control group， the model group had a significant increase in ROS fluorescence intensity （P<0.05）， and compared with the model group， there was a dose-dependent reduction in intracellular ROS level after treatment with 5 μmol/L or 20 μmol/L 2，5-DHBA （P<0.05）. Compared with the model group， 2，5-DHBA treatment at concentrations of 5 and 20 μmol/L significantly downregulated the mRNA expression levels of the lipogenic genes SREBf1 and FASN and upregulated the mRNA expression levels of the key antioxidant gene Nrf2 and its downstream target gene HO-1 （all P<0.05）. Compared with the control group， the expression of p-PI3K/PI3K and p-Akt/Akt in the model group was significantly increased （all P<0.05）. Compared with the model group， the protein expression levels of p-PI3K/PI3K and p-Akt/Akt were significantly decreased after 5 μmol/L 2，5-DHBA treatment （P<0.05）. Compared with the control group， the expression levels of Nrf2 and HO-1 protein in the model group were significantly decreased （all P<0.05）. The protein levels of Nrf2 and HO-1 were significantly increased after treatment with 1.25 μmol/L 2，5-DHBA （P<0.05）. ConclusionNetwork pharmacology and cellular experiments confirm that 2，5-DHBA can alleviate lipid deposition and oxidative stress by regulating the PI3K/Akt signaling pathway， thereby exerting a therapeutic effect on MAFLD.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

The surgical treatment of thoraco-abdominal aortic aneurysm (TAAA) requires a unique multidisciplinary approach. A thorough preoperative examination and evaluation are essential to determine the optimal timing for surgery and to optimize organ function as needed. During the perioperative period, excellent surgical skills and an appropriate strategy for extracorporeal circulation will be employed based on the extent of the aneurysm. Additionally, necessary measures will be taken to monitor and protect the functions of vital organs. Close monitoring and management in the postoperative stage, along with early detection of complications and effective treatment, are crucial for improving the prognosis of TAAA surgery. This article reviews the current research progress in the perioperative management of TAAA surgery.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.